Subcutaneous heparin treatment increases survival in small cell lung cancer

Abstract

Background. A positive influence of anticoagulant treatment in small cell lung cancer (SCLC) has been sug gested by experimental and clinical data. Methods. In a multicenter clinical trial, 277 patients with SCLC were randomized either to receive or not to receive subcutaneous heparin injections for 5 weeks at effective doses, which were monitored by blood coagulation tests. All patients received one of the two chemotherapy regimens studied in this trial, for eight courses in the case of patients with complete or partial response, and subsequently were randomized to receive delayed thoracic radiotherapy after these eight courses. Results. In comparison to the 139 patients who did not receive heparin, the 138 patients who received anticoagulant treatment obtained better complete response rates (37% vs. 23%, P = 0.004), better median survival (317 days vs. 261 days, P = 0.01), and better survival rates at 1, 2, and 3 years (40% vs. 3070, 11% vs. 9% and 9% vs. 6%, respectively). At subgroups analysis, the results on survival were obtained for limited forms (P = 0.03) but not for extensive diseases ( P = 0.31). No important bleed ing or thrombocytopenia was related to heparin treatment. Conclusions. These results confirm the value of anticoagulant treatment in SCLC, already suspected for warfarin and now proven for heparin, but the modes of administration and the biologic explanations for this activity still warrant further investigation.

Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis

“…[9][10][11][12]. A few clinical trials also suggested a beneficial effect of heparin in humans with cancer (13)(14)(15)(16)(17). However, heparin therapy can be difficult to manage on an outpatient basis and is associated with some complications.…”

Role and regulation of the thrombin receptor (PAR-1) in human melanoma

“…In addition, anticoagulant drugs warfarin and/or heparin were used in animal tumor models with positive results (Ornstein and Zacharski, 1999). Controlled clinical trials using these drugs were initiated and have produced encouraging outcomes, warfarin and heparin both prolonged the length of survival of patients with small cell carcinoma of the lung and malignant melanoma (Lebeau et al, 1994;Thornes et al, 1994). These findings suggest a potential role for thrombin inhibitors in cancer therapy.…”

Roles of vimentin and 14-3-3 zeta/delta in the inhibitory effects of heparin on PC-3M cell proliferation and B16-F10-luc-G5 cells metastasis

“…Two trials (FAMOUS and MALT) previously studied the effect of unfractionated heparin (UFH) [4] or low molecular weight heparin (LMWH) [5] in patients with small cell lung cancer. In both of these studies, a statistically significant survival advantage was observed in patients randomized to chemotherapy plus UFH or LMWH relative to patients who received chemotherapy alone.…”

“…The effect of heparin on tumors includes interference with cancer-induced hypercoagulation, cancer cell proliferation, degradation of the extra-cellular matrix (involving the heparan sulfate chains of cell surface and extracellular matrix proteoglycans), angiogenesis, selectin-mediated binding of platelets and cancer cells, growth factors and their receptors, hepara- nase, tumor progression, and metastasis [13,14] . Heparin was proposed to have a role in maintaining the effects of chemotherapeutic drugs, as both UFH and LMWH have been shown to act as chemotherapy sensitizers [4,5] . In our evaluation of the influence of heparin on tumor cell proliferation, cell cycle and apoptosis, we found that it could inhibit proliferation of PC-3M tumor cells and arrest them in the G 0 /G 1 phase.…”